The proposed research aims to elucidate the basic general function of septin proteins in multicellular organisms, specifically in Drosophila melanogaster. A role for septins, which are multidomain GTPases that form filaments, is established in yeast cytokinesis; however there are hints that septins have more general roles in directed membrane insertion and organization of the cell cortex. Through generation and examination of mutant Drosophila strains defective in particular septins, a broader definition of septin function in different cell types will be established. A second goal of the proposed research is to dissect the biological relationship between septins and conjugation to ubiquitin-like proteins of the Smt3p family. Genetic manipulation in the yeast Saccharomyces cerevisiae will distinguish whether septin subcellular localization depends upon conjugation to an Smt3p moiety, or whether septins modulate Smt3p conjugation to other proteins. One molecular mechanism by which septins participate in cortical organization will thus be elucidated.